Accession Number:

ADA357326

Title:

The Role of PKC in Retinoic Acid Regulation of Human Mammary Cancer Cell Proliferation.

Descriptive Note:

Annual rept. 1 Sep 97-31 Aug 98,

Corporate Author:

COLUMBIA UNIV NEW YORK

Personal Author(s):

Report Date:

1998-09-01

Pagination or Media Count:

35.0

Abstract:

The data presented in this annual report for award DAMDI7-96-I-6022 support our hypothesis for a mechanism of retinoic acid -induced growth arrest of human breast cancer cells. Specifically we believe that retinoic acid induced growth arrest of human breast cancer cells requires protein kinase Ca expression. The constitutive expression of PKCa in hormone independent, MDA-MB-231 cells induced retinoic acid sensitivity to inhibit the uncontrolled proliferation and to alter the proto-oncogene expression. Retinoic acid treatment in PKCa expressing MDA-MB-231 cells reduced 40 of cell proliferation and inhibited serum induction of c-fos expression. Concomitantly, c-jun expression was enhanced. These findings, along with the observation that retinoic acid treatment enhanced PKCa expression, conventional PKC activity and translocation of PKCa to cell membrane and nucleus, raised the possibility that PKCa induced retinoic acid sensitivity in MDA-MB-231 cells is caused by disturbance of mitogenic signaling or trancriptional regulation of target genes. By turning onoff the transcription of PKCa gene, we further demonstrated the PKCa regulation of c-fos and c-jun expression. In total, we demonstrate that the lack of anti-proliferation effect of retinoic acid in MDA-MB-231 cells is caused by the failure of RA induced PKCa expression and subsequent absence of PKCa altered gene expression.

Subject Categories:

  • Medicine and Medical Research
  • Pharmacology

Distribution Statement:

APPROVED FOR PUBLIC RELEASE